BOVINE VIRAL
DIARRHEA – MUCOSAL DISEASE
(BVD-MD)
• BVDV is involved in a wide range of clinical syndromes including respiratory, intestinal and reproductive disease. It has also been shown to cause the fatal condition of MUCOSAL DISEASE.
• It causes;
• weight loss in animals,
• decrease in milk yield,
• death in 4-8%,
• leucopenia,
• high fever,
• salivation,
• nasal discharge,
• diarrhea,
• depression and
• abortion in pregnant cows.
• The most affected age group is 3-8 months. The virus is widespread; about 60-70% of adult cattle have experienced a BVDV infection by 4 years of age.
Systemic infection
Etiology
• Flaviviridae--- Pestivirus
• RNA
• Enveloped
• HA
• Sensitive to Ether and Chloroform
• The virus could be cultivate only in primer and fetal cell cultures
• BVDV exists in two different forms (biotypes) in the field; either non- cytopathogenic (BVDVnc) or cytopathogenic (BVDVc) virus. They are distinguished by their cytopathogenic effect when grown in cell culture.
The two biotypes have different roles in the pathogenesis of BVDV infections.
• Reference strain is NADL.
• This virus may cause PERSISTENT INFECTION.
• BVDV is an RNA virus and is closely related to the classical swine fever virus (CSFV) and the Border disease virus of sheep (BDV).
• All three viruses can induce cross-reacting antibodies to each other but there is evidence for a closer antigenic relationship between BVDV and BDV. Cross infection between cattle and sheep has been recorded.
• Although the name may suggest that BVDVc isolates are more pathogenic, it is the BVDVnc viruses that are more important as a cause of disease.
• BVDVnc can cross the placenta and establish a persistent infection.
(PI) in the foetus which is lifelong.
Transmission
• The major source of BVDV is without doubt the persistently infected (PI) animal.
• However, spread of virus by DIRECT CONTACT with acutely infected animals is also important. Other sources of BVDV can be semen,
unscreened biological products, and transmission through repeatedly used hypodermic syringes and needles. Multiple use of rectal gloves is also a potential source for virus transmission.
• This viral infections could spread with blood, nasal discharge, saliva, tears, semen, milk, feces, urine, uterine fluids, amniotic fluid and membranes of infected animals.
• INDIRECTLY, feed, drinking water, barn staff and vehicles play a role in the transmission of the disease.
• BVDV can infect cattle at any age.
• It is usually a mild disease with recovery by 10 days. However, it can play a key role in calf respiratory disease and enteritis. By causing immunosuppression, the virus facilitates other pathogens to produce more severe disease e.g. IBR, RSV & Salmonella.
• In some outbreaks, BVDV can cause more serious disease with diarrhoea, anorexia and agalactia.
Pathogenesis and Pathology
• The virus enters the organism by oral route.
• Virus replicates in nose and nasal cavity epithelium, mouth cavity, larynx, pharynx and intestinal epithelium
• Virus passes through the placenta in pregnant animals and could infect the fetus.
• The infection causes A.H syndrome (arthrogryposis-hydranencephaly), Photopathy, eye disorder and cerebellum hypoplasia in fetus.
• Histopathologically,
• epithelial cell necrosis and inflammation
• Pathologically
• erosions occur in the mucous membranes,
• and ulcers occur in the mouth, palate, gingiva and larynx.
Clinical Signs
• Fever, anorexia, watery diarrhea, pneumonia and erosive stomatitis occur.
• In non-pregnant cattle:
- The incubation period is 5-7 days.
- The infection begins with fever and leukopenia.
- The infection could be subclinical.
- The infection could cause diarrhea, nasal and ocular discharge and a decrease in milk yield.
- The infection, transmitted through the sperm of persistently
infected bulls, could cause embryo deaths.
• Infection in Pregnant Cows:
• Infections before the 100th day of pregnancy usually lead to death and low birth weight and cause developmental
disorders in organs.
• Animals that are infected intrauterine before the
development of immune ability (immuncompetant) are the source of infection throughout their lives.
• Their sera results as negative in serological tests.
If the pregnancy is between 100-
150 days; There are disorders in
the central nervous system in the
eyes.
CERBELLAR HYPOPLASIE
Calf without Cerebellum
LUNG HYPOPLASIS
MICROPHTALMUS
ALLOPECIA
Abortus caused by BVDV
Gingival Lesions
• Persistently Infected Cattle:
a) They are persistently infected with BVDVnc and never BVDVc.
b) They rarely make antibody to the persisting virus.
Therefore, they are often antibody negative to BVDV:
However, they can make antibody to other BVDV
isolates that are 'heterologous'to the persisting virus.
As a result, they can have low level of BVDV antibodies to 'heterologous' virus.
c) The clinical appearance of P.I. animals can range from:severe congenital damage (eg ataxia) to unthrifty and increased susceptibility to
respiratory/enteric diseases to clinically normal.
- Chronic fever, anorexia, watery diarrhea, nasal discharge and erosive-ulcerative stomatitis, dehydration, vomiting and death could occur in calves.
Not infected PI
d) They represent the main reservoir for BVDV in the herd and;
therefore, must be identified. The only way to do this is to assay for either infectious virus (cell culture or IPX) or by antigen capture (ELISA).
e) Only PI animals will surrender to fatal mucosal disease. There is no known treatment to reverse the persistent infection. Vaccination will not prevent PI animals from contracting mucosal disease (However, vaccination of dams before pregnancy should prevent their foetuses becoming PI).
Mucosal Disease
• Mucosal disease is a fatal condition of cattle, characterised by oral and enteric erosions, which overlie the Peyer's patch lymphoid areas.
Animals can die very rapidly but typically they show signs of anorexia, depression and diarrhoea for 2-5 days before death. Sometimes a
longer period is reported. They do not respond to treatment.
• The pathogenesis of mucosal disease is complex and has shown interacting roles for both biotypes of the BVD virus. The chronology of events is crucial.
• At the initiation of immuno-competence, the established virus appear be treated as 'self and all clones of immune cells, reactive to BVDV, are depleted. This depletion tolerance would account for the failure of the animal to make BVDV antibody to clear the virus. They are persistently infected for life.
The initial event is an infection of the susceptible (sero-negative) dam in early pregnancy the virus biotype, ALWAYS BVDVnc, will cross the placentome and
establish in the foetus. Before 110 days, the foetus is not
immunologically competent and cannot recognise or eliminate the virus.
• The second event is the superinfection of PI animals with the second biotype, BVDVc.
• This usually occurs between 6-18 months old but can occur within weeks of birth and as late as 7-8 years old.
• Following superinfection, the animal develops fatal mucosal disease within 3 weeks. It is now evident that antigenic 'homology' between the two biotypes is important for the rapid onset of mucosal disease.
• Once BVDVc has arisen, it will spread quickly amongst PI animals by direct contact.
The cause of MD
• BVDVnc
• early foetal infection before 110 days
• PI foetus - fetal immunotolerance
• Birth of PI calf - calf antibody (-), antigen (virus) (+)
• PI animal, (usually about 6-18 months old)
Mutation or Superinfection with BVDVc
rapid onset of clinical disease
Diagnosis
• Isolation of BVDV virus from;
• Leukocyte, Nasal Flow, Feces, Spleen, Lymphoid nodes, Bowel, Cotyledon, Fetal Liver and Kidneys.
• Immunofluorescence (IF)
• Immunperoxidase
• ELISA
• PCR
Serologic Antigenic
ELISA
Neutralization
Neutralizing Immunofluorescence Neutralizing Immunoperoxidase
PI animals are antibody negative whereas they are virus positive.
An important exception is that PI calves often appear virus negative in blood for 3-4 months, following ingestion of colostrum.
• 21 days after the first blood sample, blood is taken again to check whether the infection is persistent or acute.
• If the second blood sample is virus (+) and Ab (-) that means persistent infection.
• If opposite virus (-) Ab (+) means Acute infection.
Abs negative, virus positive points the persistent infection
Immunology
• The placenta in the Syndesmochorial structure does not allow to pass the maternal Abs to the calves during the pregnancy.
• Therefore, maternal Abs are transferred to the calves by colostrum.
• Neutralizing Abs against BVDV have been detected from 90- 168 days of pregnancy.
• In the early stages of the pregnancy, immunetolerance is formed in fetus.
• After the infection Neutralizan, complement fixing and
Precipitating Abs occur.
Prevention and Control
• There is no cure.
• Antibiotic treatment could be used against seconder bacterial infections.
• There are lived-modified tissue culture vaccines in some countries.
Usually they are implemented after 6-9 months old age.
• The best way forward is to vaccinate females of breeding age before they are inseminated. This will prevent the considerable reproductive loss due to the virus, ensure that unborn calves are not prematurely exposed to BVDV and become persistently infected. This will, in turn, remove the main reservoir of viral infection for other cattle.
BORDER DISEASE
• The newly born lambs are characterized by dulled feathers, CNS disorders, lower birth weight, and changes in the skull skeleton.
• Infection in ewes and goats, occasionally cattle, is not commonly clinical, unless the animals are pregnant.
• Can cause significant abortion in individual flocks (associated with focal necrotising placentitis) and congenital abnormalities in lambs.
ETIOLOGY
• Flavivirdae --- Pestivirus
• RNA
• Enveloped
• Sensitive to Ether and Chloroform
• HA
• The virus could be cultivate in primer and fetal cell cultures
• This virus may cause PERSISTENT INFECTION. (till 60-80 days of pragnancy)
• is closely related to the classical swine fever virus (CSFV)
and the BVDV.
• Dams infected one season appear to be immune to subsequent infection. Persistently infected lambs that survive are a source of infection to other sheep.
• There is evidence that BVDV from cattle can infect sheep and give rise to disease as described for BDV.
• Persistent infections are important.
• In general, transmission of the infection is Direct and Indirect.
• Tear, Nasal Drain, Feces, Urine, Uterine Flow, Amniotic Fluid, Plesenta and Semen contain virus.
Vertically transmitted infection is when disease is transmitted from one generation to another and can be either in
utero via the placenta, or lactogenically, via the mother’s milk. Horizontal transmission is disease transmission from one animal to another.
Pathogenesis and Clinical Signs
• Non-Pregnant ewes:
- infection could be subclinical
- Fever, short-period lymphopenia and viremia are seen.
- Also depression, diarrhea.
• Infection in pregnant ewes:
- Ewes show no clinical signs.
- The virus spreads on the placenta. The fetus infected at the end of the first week.
- Infection causes abortion, weak lamb births
- Although the immun system of the ewes eliminates all virus from the tissues in a short period of time, the virus remains in the fetus
persistently.
• Fetal Infection :
- Severity of infection depends on the strain, dose, nutrition.
- The most dangerous time for the fetus is to get infected in the first 80 days of the pregnancy (before immun system develops)
- The reasons of the persistent infections;
1-The placenta of the ewes does not allow to pass through the antibodies to the fetus.
2-Since the immunity system of the fetus does’t develop in this period, the immun response does not occur.
3- Depending on the infections period, pathological lesions occur.
• Persistenly infected lambs:
- It occurs during the first 80 days of intrauterine life of lambs.
- Classical outcome of in utero is the 'hairy shaker' lamb.
- So we can say that the tropism of the virus and the other pestiviruses are for foetal lymphoid, skin and CNS tissues. 'Hairy shaker' lambs have hair rather than wool coats and CNS lesions often with
hypomyelinogenesis and hypocerebellum. (AH SYNDROME)
- Often there is in utero growth retardation (IUGR) in skeletal tissues and some lambs are born weak and most do not thrive. Some are persistently infected with the virus.
Weak lambs naturally infected with Border disase virus. Affected lambs showed: (a) growth retardation. (b) ocular and nervous signs. (c) nervous signs and (d) locomotor disturbances.
Clinical and pathological observations of diseased goats. A. diseased goat showed
depression, rough hair-coat and growth retardation; B. goat with diarrhea. The anus and neighboring fur were covered with loose stool; C and D. hemorrhage and necrosis in small and large intestine (black arrows)
Published in Virology Journal 2012 Detection of border disease virus (BDV) in goat herds suffering diarrhea in eastern ChinaWenliang Li, Long Mao, Yongqian Zhao, Yinhua Sun, Kongwang He, Jieyuan Jiang
Summary
• In the sheep, mild fever and leukopenia occur.
• Infections pass through to fetus in pregnant ewes and abortion and birth anomalies are seen.
• It may causes P.I animals
• Abort events mostly occur on the 90th day. Fetus is Brown, mummfied and swollen.
• Early-born lambs can not stand up, there are the appearance of «hairy shaker»
• Pigmentation is in the neck.
• A.H syndrome
Diagnosis
• This is usually subsequent to clinical diagnosis of abortion and the birth of 'hairy shaker' Iambs.
• Detection of Ab by ELISA
• Netralization
• virus by virus isolation in cell culture
• Antigen detection in ELISA are the common methods for BVD diagnosis.
• IF, IP for Non-CPE virus
Abs negative, virus positive points the persistent infection
Prevention and Control
• Imported animals must be checked for the disease
• Slaughter is recommended in sporadic cases.
• Persistently infected animals in endemic cases must be eliminated
• 2 months before breeding, all animals should be serologically control.
• 21 days after the first blood sample, blood is taken again to check whether the infection is persistent or acute.
• If the second blood sample is virus (+) and Ab (-) that means persistent infection.
• If opposite virus (-) Ab (+) means Acute infection.
• There are vaccines in the USA and in Europe. Control can
only be by careful screening of sheep to be introduced into
clean flocks or by the screening of suspected clinical cases.
LOUPING ILL
DISEASE
• Louping ill is a tick-borne, zoonotic, viral disease that is mostly important in sheep and red grouse.
• Severe clinical signs can be seen in naive sheep flocks moved into endemic areas. Many animals may develop neurological disease, and up to 60% of the flock can die.
• Cases of louping ill are also reported occasionally in other species including goats, lamas, alpacas, swine, horses and deer.
• Humans can develop flu-like symptoms or neurological signs after exposure, but the illness is rarely fatal.
Etiology
• Flaviviridae ---- Louping ill virus
• Four subtypes of louping ill virus – the British, Irish, Spanish and Turkish
subtypes – have been identified; however, a recent genetic analysis suggests that the Turkish subtype (Turkish sheep encephalitis virus) is more closely related to TBEV than louping ill virus, and should be reclassified.
• RNA
• Enveloped
• HA (with duck erythrocyte)
• Sensitive to Ether and Chloroform
• Virus, tissue culture; Monkey, Lamb, pig kidney cells
Chicken embryo Fibroblast
BHK-21 (CPE)
E. A.; Mice, Rattus,Hamster
Transmission
• Sheep are the most important hosts for louping ill virus.
• Louping ill is transmitted mainly by ticks.
• The principal vector is the three-host tick Ixodes ricinus.
• Transstadial transmission and overwintering of the virus have been
documented in this species, but transovarial transmission does not seem to occur. Several other species of ticks including Rhipicephalus appendiculatus, I. persulcatus and Haemaphysalis anatolicum are also capable of transmitting louping ill virus, but they do not seem to be important in the epidemiology of this disease.
• Only sheep and red grouse consistently develop viremia sufficient to infect ticks and amplify the virus.
• Louping ill virus can also be transmitted by other routes. This virus is shed in the milk of goats, and to a lesser extent, sheep; lambs and kids may become infected when they nurse.
Pathogenesis and Pathology
• Cyclic disease. The fever rises with the viremia and the virus multiplies in the lymph glands and spleen.
• Five days after the onset of the clinical symptoms virus pass through to CNS.
• Histopathologically, infection causes;
• encephalomyelitis,
• meningitis,
• neuronal degeneration in the purkinje cells and
• hyperemia
Clinical Signs
• The incubation period for louping ill is 6-18 days in sheep.
• Two-phase fever is observed.
• In sheep, louping ill is characterized by an initial febrile viremic stage, which may be accompanied by depression and anorexia, followed in some cases by neurological signs.
• Spasms are typical.
• In endemic areas, many animals develop mild or subclinical infections.
• In animals with encephalitis, the clinical signs may include
• muscle tremors and/or rigidity,
• incoordination,
• ataxia,
• hypersensitivity,
• salivation and nervous nibbling,
• progressing in some cases to head pressing,
• posterior paralysis,
• recumbency,
• convulsions and/or coma.
• Affected sheep may develop an unusual hopping gait, called a
“louping gait,” during which they move both hindlegs, then both forelegs, forward in unison.
• Death is common among animals with neurological signs, often within a few days.
• Peracute deaths can also be seen.
• Surviving animals may have residual CNS deficits.
Diagnosis and Differential Diagnosis
• It is difficult to diagnose clinically.
• Louping ill should be suspected in sheep with fever and neurological signs, particularly when the flock has recently been introduced to tick–infested pastures.
• Scrapie, pregnancy toxemia, maedi–visna, rabies, tickborne encephalitis virus (TBEV), coenurosis, listeriosis, hypocalcemia,
hypocuprosis and various toxicities are among the considerations in sheep.
Louping ill can be diagnosed by virus isolation,
the detection of viral nucleic acids or antigens serology.
•Louping ill virus may be recovered from the blood during the acute phase of the disease, or from the brain and spinal cord of animals with neurological signs. This virus can be isolated in porcine or ovine kidney cell lines, as well as in embryonated eggs.
•It may also be recovered by intracerebral inoculation of suckling mice.
• Viral antigens or nucleic acids can be detected in the CNS by immunohistochemical staining or with a RT–PCR assay,
respectively.
• Histopathology can be helpful.
• Serological tests include
• hemagglutination inhibition,
• serum neutralization,
• ELISA
• complement fixation.
• The detection of virus specific IgM in the hemagglutination inhibition test indicates that the infection is recent.
• Cross-reactions can occur with other flaviviruses in
serological tests.
Immunology
• In endemic areas, the mortality rate is usually 5–10%, and most cases occur in animals that are less than two years old.
• Lambs born in these areas are usually protected by maternal
antibodies for the first few months of life, and older animals have developed immunity.
Prevention and Control
• In endemic regions, sheep can be protected by vaccination, or by preventing exposure to habitats where ticks are found.
• Lambs born to vaccinated or naturally infected ewes are usually protected by maternal antibodies for the first few months of life.
• Vaccines have also been used in cattle and goats.
• Acaricides can reduce tick populations, but it is difficult to protect animals by this method alone.
Louping Ill in Humans
• Humans can be infected via tick bites or by contact with the virus in tissues or laboratory cultures.
• Louping ill virus may be transmitted through skin wounds (working with sheep, wool), and aerosol exposure has been reported in
laboratories.
• Biphasic Fever in humans causes Influenza-like symptoms and abortions.
• The prognosis is good.
